A Prophylactic Human Cytomegalovirus (HCMV) Vaccine Designed to Prevent

Congenital Infection Using Enveloped Virus-Like-Particles (eVLPs) by Inducing Potent

Immunity Greater Than Natural Infection

ICAAC 2014, Washington, D.C.
September 7
th
, 2014
2
This presentation contains forward-looking statements within the meaning of the provisions of Section 27A
of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. Forward-looking statements are generally identifiable by the use of words like "may," "will,"
"should," "could," "expect," "anticipate," "estimate," "believe," "intend," or "project" or the negative of
these words or other variations on these words or comparable terminology. The reader is cautioned not to
put undue reliance on these forward-looking statements, as these statements are subject to numerous
factors and uncertainties outside of our control that can make such statements untrue, including, but not
limited to, inadequate capital, adverse economic conditions, intense competition, lack of meaningful
research results, entry of new competitors and products, adverse federal, state and local government
regulation, termination of contracts or agreements, technological obsolescence of our products, technical
problems with our research and products, price increases for supplies and components, inability to carry out
research, development and commercialization plans, loss or retirement of key executives and research
scientists and other specific risks. We currently have no commercial products intended to diagnose, treat,
prevent, or cure any disease. The statements contained in this presentation regarding our ongoing research
and development and the results attained by us to-date have not been evaluated by the Food and Drug
Administration. There can be no assurance that further research and development, and/or whether clinical
trial results, if any, will validate and support the results of our preliminary research and studies. Further,
there can be no assurance that the necessary regulatory approvals will be obtained or that we will be able
to develop new products on the basis of our technologies. In addition, other factors that could cause actual
results to differ materially are discussed in a Proxy Statement filed with the SEC on June 30th, 2014.
Investors and security holders are urged to read these documents free of charge on the SEC's web site at
www.sec.gov. We undertake no obligation to publicly update or revise our forward-looking statements as a
result of new information, future events, or otherwise.
Forward-Looking Statement Disclaimer
3
Introduction
Virus-like particle (VLP) vaccines have evolved considerably since their
introduction in the early 1990s.
3
RD
GENERATION VBI 1
S T
GE NE RAT I ON 2
ND
GE NE RAT I ON
Design: Antigens are produced and
self-assemble
Key Advantage: Simple structures
and repetitive pattern of antigenic
epitopes
Key Limitation: Only a very limited
number of antigens spontaneously
form orderly VLP structures; cannot
be applied to all enveloped viruses
Examples: Gardasil, Cervarix,
Engerix-B, and Recombivax HB
Design: Antigens of interest are
covalently attached to the surface
of a backbone protein
Key Advantage: Can be applied to
multiple different target antigens;
VLP structure is not limited to the
properties of the antigen
Key Limitation: Antigen of interest is
artificially bound to the structural
protein and not represented in a
natural configuration
Example: Qb VLP Platform
Design: Common protein backbone
and a lipid membrane in which the
antigen of interest can be expressed
Key Advantage: Enables a more
natural presentation of the target
antigen within a membrane that
more closely mimics a virus; can be
used to express multiple target
antigens in a single VLP
Limitation: More effort required in
purification to meet FDA/EMA
standards
eVLP Ideal Candidates: CMV, HCV,
Dengue, RSV, and West Nile
4
Antigenic
Protein
No Infectious
Genetic
Machinery
Natural Lipid
Bilayer
Antigenic protein
retains natural
conformation in
the Lipid Bilayer
Top: eVLP Diagram the foundation of the eVLP technology is a
stable, protein-based core on which additional vaccine antigens
of interest can be added; Bottom: Electron microscopy image of
VBIs CMV eVLP captured by NanoImaging Services.
eVLP Platform
eVLPs are a third-generation class of
synthetic vaccines that closely resemble the
structure of the virus they mimic.
eVL P PL ATFORM HI GHL I GHTS
Same size and structure as enveloped viruses
Present antigens in their natural state (lipid
bilayer) to provoke an optimal immune response
In animal research, demonstrated ability to
trigger strong, broadly neutralizing antibodies in
multiple preclinical models (CMV, HCV, and Flu)
Suitable to a wide array of viruses including CMV,
HCV, Dengue, RSV, and West Nile
Strong intellectual property estate
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Medical Need
Cytomegalovirus (CMV) is a common virus that can cause serious, life-
threatening complications in persons with weakened immune systems.


PERSONS L I KELY TO DEVELOP CMV COMPL I CATI ONS
Congenital CMV: Unborn babies whose mothers become infected with CMV during
pregnancy are at high risk
Congenital CMV infection causes more long-term problems and childhood
deaths than Down Syndrome or Fetal Alcohol Syndrome
In the U.S., congenital CMV causes one child to become disabled every hour
Immunocompromised: A primary CMV infection can cause serious disease in organ
and bone marrow transplant recipients, cancer patients, and patients receiving
immunosuppressive drugs
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Overview of eVLP Design and Production
eVLPs are produced after transient transfection of
cells (e.g. HEK 293, CHO, Vero) with plasmids
encoding:
MLV Gag
Extracellular domain of gB protein fused with
transmembrane (TM) domain of vesicular
stomatitis virus G protein (VSV-G)
Presence of VSV TM domain enhances targeting to
cell membrane and optimal protein conformation
(greater induction of neutralizing antibodies)
MLV Gag expression induces budding of particles
from lipid raft domain of transfected cells, with CMV
gB protein incorporated into the final eVLP structures
Formulation of eVLPs with alum phosphate (VBI-
1501A) provides product stability in vitro and
enhanced durability of immunity in vivo
MLV Gag Lipid bilayer
gB
Monovalent gB-G eVLP
Vaccine Candidate (VBI-1501)
7
VBI-1501/A were produced using a
GMP compliant HEK 293 cell line
and purified to meet FDA standards
Pooled sera from vaccinated mice
(n=8) were tested for the ability to
neutralize CMV infection in both
Fibroblast and Epithelial cells, two
clinically relevant cell types
susceptible to CMV infection
VBI-1501A: Rapid, Potent, and Durable Immunity

VBI-1501A elicits rapid, potent, and durable neutralizing
antibody titers, which exceed naturally acquired levels of
immunity (Cytogam) after two immunizations (weeks 0 and 8)
in mice.
1
10
100
1,000
10,000
0 4 8 12 16 20 24 28 32
E
p
i
t
h
e
l
i
a
l

c
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l
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n
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b

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(
1
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)

1
10
100
1,000
10,000
0 4 8 12 16 20 24 28 32
F
i
b
r
o
b
l
a
s
t

c
e
l
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n
A
b

T
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1
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Time (weeks)
VBI-1501 VBI-1501A [alum] Cytogam
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Successful Optimization of Yield at GMP
Manufacturer


Optimization study
improved gB yield ~4X
while maintaining
optimal gB/Gag ratio
Optimization study improved gB yield ~4X while maintaining optimal
gB/Gag ratio
g
B

(
n
g
/
m
l
)

g
B
/
G
a
g

r
a
t
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o

9
Regulatory Compliant Purity Achieved
eVLP Purification Scheme
Centrifuge
Remove cells/debris
Tangential flow filtration
Purify eVLPs from soluble proteins
Benzonase/PL Tx & diafiltration
Inactivate/remove residual DNA
Ultracentrifugation
Purify eVLPs from residual host cell
proteins
Sterilize (filter)
SDS-PAGE of VBI 1501
Full length gB-G
C-terminus gB-G
N-terminus gB-G
High Molecular Weight Gag
High Molecular Weight Gag
Full Length Gag
Gag Cleavage
Gag Cleavage
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CMV Program Summary
Rapid, potent and durable immunity demonstrated with both drug substance (VBI-
1501) and drug product (VBI-1501A)
Pilot scale(10L) production of VBI-1501 meets Phase I release criteria
gB to Gag Ratio a key determinant of potency
Purity:
Residual DNA: Target <10ng/dose Actual: 5.8ng/dose
Residual HCP: Target <500ng Actual: 5ng/dose
Stability:
Confirmed in vivo stability of drug substance (VBI-1501) after 6 mo @ -20C
Planned IND submission / Phase I start in Q4 2015
11
Acknowledgements
Catalina Soare
Jasminka Bozic
Barthelemy Ontsouka
Tanvir Ahmed
Abebaw Diress
Melissa Lemieux
Matthew Yorke
Isabel Yang
Diana Duque
Adam Asselin
Anne Catherine Fluckiger
Marc Kirchmeier
Scientific Advisory Board
VBI Vaccines, Inc.
222 Third Street, Suite 2241
Cambridge, MA 02142
(617) 830-3031
info@vbivaccines.com